Unlocking nature's antioxidants: a novel method for synthesising plasmalogens.

Plasmalogens are glycerophospholipids distinguished by their -()-vinyl ether at the -1 position. These lipids are implicated in several disease states requiring analytical, diagnostic and therapeutic interventions, which demand synthetic availability for a variety of structural types. By deploying the new -protecting group 1,4-dimethoxynaphthyl-2-methyl ('DIMON') and a new stereospecific method for accessing -vinyl ethers, a reproducible, versatile synthetic route to plasmalogens [plasmenyl phosphocholines] has been developed. A key intermediate is (,)-1-((1,4-dimethoxynaphthalen-2-yl)methoxy)-3-(hexadec-1-en-1-yloxy)propan-2-ol, which in principle, permits plasmalogen synthesis 'à la carte' at scale. The methodology compares favourably with all previous synthetic routes by virtue of the very high configurational (>99% ) and optical purity (>99% ), including the ability to incorporate polyunsaturated fatty acyl chains ( all docosahexaenoic acid) reliably at the -2 position.